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Updated: Mar 14, 2026
Isolation and Culture Expansion of Tumor-specific Endothelial Cells
Published on: October 14, 2015
Ion channels expression and function are strongly modified in solid tumors and vascular malformations
Antonella Biasiotta1, Daniela D'Arcangelo2, Francesca Passarelli2
1Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
Background:
Several cellular functions relate to ion-channels activity. Physiologically relevant chains of events leading to angiogenesis, cell cycle and different forms of cell death, require transmembrane voltage control. We hypothesized that the unordered angiogenesis occurring in solid cancers and vascular malformations might associate, at least in part, to ion-transport alteration.
Methods:
The expression level of several ion-channels was analyzed in human solid tumor biopsies. Expression of 90 genes coding for ion-channels related proteins was investigated within the Oncomine database, in 25 independent patients-datasets referring to five histologically-different solid tumors (namely, bladder cancer, glioblastoma, melanoma, breast invasive-ductal cancer, lung carcinoma), in a total of 3673 patients (674 control-samples and 2999 cancer-samples). Furthermore, the ion-channel activity was directly assessed by measuring in vivo the electrical sympathetic skin responses (SSR) on the skin of 14 patients affected by the flat port-wine stains vascular malformation, i.e., a non-tumor vascular malformation clinical model.
Results:
Several ion-channels showed significantly increased expression in tumors (p < 0.0005); nine genes (namely, CACNA1D, FXYD3, FXYD5, HTR3A, KCNE3, KCNE4, KCNN4, CLIC1, TRPM3) showed such significant modification in at least half of datasets investigated for each cancer type. Moreover, in vivo analyses in flat port-wine stains patients showed a significantly reduced SSR in the affected skin as compared to the contralateral healthy skin (p < 0.05), in both latency and amplitude measurements.
Conclusions:
All together these data identify ion-channel genes showing significantly modified expression in different tumors and cancer-vessels, and indicate a relevant electrophysiological alteration in human vascular malformations. Such data suggest a possible role and a potential diagnostic application of the ion-electron transport in vascular disorders underlying tumor neo-angiogenesis and vascular malformations.
Insights
Altered ion channel activity is linked to cancer and vascular malformations. This study identified specific ion channel genes with altered expression in tumors and electrophysiological changes in vascular malformations, suggesting diagnostic potential.
Area of Science:
- Oncology
- Molecular Biology
- Physiology
Background:
- Cellular functions, including angiogenesis and cell death, depend on transmembrane voltage control.
- Altered ion transport may contribute to abnormal angiogenesis in cancers and vascular malformations.
Purpose of the Study:
- To investigate the association between ion channel alterations and the development of solid tumors and vascular malformations.
- To identify specific ion channel genes with altered expression in various human cancers.
- To assess electrophysiological changes in vascular malformations.
Main Methods:
- Analyzed expression of 90 ion channel genes in human solid tumor biopsies from 3673 patients across five cancer types using the Oncomine database.
- Measured in vivo sympathetic skin responses (SSR) in 14 patients with port-wine stains to assess ion channel activity.
Main Results:
- Significantly increased expression of several ion channels was observed in tumors (p < 0.0005).
- Nine specific ion channel genes (CACNA1D, FXYD3, FXYD5, HTR3A, KCNE3, KCNE4, KCNN4, CLIC1, TRPM3) showed significant modification in at least half of the datasets for each cancer type.
- In vivo studies revealed significantly reduced SSR in port-wine stain affected skin compared to healthy skin (p < 0.05).
Conclusions:
- Identified ion channel genes with significantly modified expression in tumors and cancer-associated vasculature.
- Demonstrated relevant electrophysiological alterations in human vascular malformations.
- Suggests a potential diagnostic role for ion-electron transport in vascular disorders underlying tumor angiogenesis and malformations.
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